Dairy Reproduction: More Progesterone, Please

Modern dairy cows have issues with steroids. One particular steroid they could use more of at times is one that has a calming effect, both inside and outside. This steroid hormone is called progesterone. It is essential for normal reproductive cycling, inhibits estrus (that often-crazy outward behavior), and controls the growth of follicles on the ovaries (inside).

Where does progesterone come from? Under natural circumstances, it is produced by the corpus luteum (CL), the ovarian structure that forms from an ovulated follicle. Progesterone generally goes into circulation in high enough concentrations to maintain a pregnancy, among a host of other important effects. Progesterone can be supplemented through reproductive management efforts, most commonly by a controlled internal drug release (CIDR) insert, whether as part of a synchronization protocol or simply a prescribed treatment for problem cows.

In high-producing cows, circulating concentrations of progesterone are sometimes lower than ideal. As cows produce more milk, they eat more. When they eat more, their metabolism tends to be greater. With higher metabolism, which includes higher blood flow, progesterone is broken down more rapidly in the liver. And these high-producing cows don’t simply develop larger CL to produce more progesterone and counteract the disappearance of progesterone. Thus, progesterone concentrations can oftentimes drop below optimum levels.

There are two key situations in which a modern dairy cow, particularly high-producing Holsteins, stand to benefit from more progesterone: during follicle development and during a small window of early pregnancy.

Progesterone during follicle development

It is becoming increasingly clear how critical is it for lactating cows to have high circulating concentrations of progesterone during the luteal phase of the estrous cycle PRIOR to ovulation and insemination. Not only does progesterone have a priming effect on the uterus for pregnancy, but it has a significant effect on the quality of the developing follicle and oocyte housed inside of it, with higher progesterone concentrations leading to improved embryo development (Pereira et al., 2017).

Because of progesterone’s controlling and somewhat suppressive effects on luteinizing hormone, one of the key hormones stimulating follicle growth, lower concentrations of progesterone in the circulation generally result in larger follicles. Ovulation of these larger follicles leads to lower conception rates when compared to follicles which have developed in an environment with more progesterone due to poor oocyte and embryo quality (Denicol et al., 2012). This is the case even though those larger follicles tend to become larger CL and produce more progesterone after ovulation.

It was shown in a recent study, when pregnant cows were compared to open cows, the pregnant cows had a larger luteal area in the middle of the cycle immediately preceding insemination (Berger et al., 2017). Larger CL and more progesterone play a critical role.

This issue of compromised progesterone creates a particular problem when a timed AI protocol such as Ovsynch is used with anovular cows, or when it is initiated during the first follicular wave of the estrous cycle. In both cases there is not a sizeable CL present at the beginning of the protocol, thus progesterone concentrations are low.

The good news is that supplementation of progesterone during a timed AI protocol increases conception rates by approximately 10% (Bisinotto, 2015). Supplementation is especially effective in cows without a CL at the initiation of the timed AI program. It decreases pregnancy loss, presumably causing changes in the uterus that increase embryo development and long-term viability (Wiltbank et al., 2014).

Progesterone during early pregnancy

Supplementation of progesterone during the period of three to seven days post-insemination results in significantly improved conception rates (Garcia-Ispierto and López-Gatius, 2017), particularly when herd conception rates tend to be low (Yan et al., 2016). There are minimal proven benefits of supplemental progesterone after that first week post-insemination, despite many efforts to discover them.

Twinning

Low progesterone may be one of the key reasons that twinning is such a challenge in the modern dairy cow. When progesterone is low during follicle development, there is a higher likelihood for codominance of two follicles and double ovulation, which can lead to twinning (Fricke, 2015). With higher progesterone, the risk is much less.

Interestingly, there is another risk period for twinning. Providing progesterone supplementation on Days 15 to 17 post-insemination, a critical time for maternal recognition of pregnancy and a time when it might be expected that extra progesterone would be beneficial, significantly increases the frequency of twin pregnancies, presumably by saving one of the two that might have been lost had progesterone not been supplemented (Garcia-Ispierto and López-Gatius, 2017). That is a risk most dairy managers would prefer to avoid.

So what can be done to manage for better progesterone and fertility? It is usually beneficial to identify key groups of cows and key times when they would most benefit from treatment. And two of the valuable tools for accomplishing this are GnRH products and CIDRS.

Treatment with GnRH is a safe and often cost effective way to cause ovulation (i.e. increase progesterone), often effective even with anovular cows. When incorporated into a timed AI protocol at strategic times, it can be very effective in controlling follicular wave patterns and providing the progesterone needed to prime for pregnancy. Even in a herd relying primarily on heat detection, there is likely a place for GnRH in managing for reproductive success.

Using CIDRs ensures that progesterone will be present in the cow. A single CIDR does not bring progesterone concentrations up to what they would typically be with a normal, functional CL, but is still effective. Due to the higher cost and management requirements with CIDRs, they may be best used on a selective basis, targeting the anovular cows and other problem cows which have not been identified in estrus or don’t seem to be cycling normally.

Lastly, it should be clarified that circulating progesterone concentrations should not always be high. After prostaglandin treatment and around the time of AI, progesterone should be low. This change is critical for reproductive success.

In the modern dairy cow, progesterone, an all-important steroid hormone, is one to keep an eye on.